Generally, prolactin (PRL) is a 199 amino acid protein which is normally produced by the pituitary throughout an animal's life. PRL plays a role in the development of mammary tissue in females and, during pregnancy, produces a further development of mammary tissue and stimulates the production of milk. Although known for its mammatropic and lactogenic effects, PRL is generally not considered an efficient anabolic agent. In addition, PRL is considered species specific. Human, ovine, and porcine PRL have 144 of their 199 residues in identical positions but neither the ovine nor porcine PRL is active in humans.
PRL has been isolated from excised pituitary tissue. See, e.g., Li et al., Nature, 224, 695-696 (1963) (ovine); Lewis et al., Biochem Biophys. Res. Commun., 44(5), 1169 (1971) (human); Reisfeld et al., J. Am. Chem. Soc., 83, 3719 (1961) (sheep); and Li et al., J. Biol Chem, 146, 627 (1942) (ox, sheep and swine) PRL can also be obtained from genetically engineered microorganisms containing recombinant DNA which specifies the production of PRL using well known techniques. For example, the nucleotide coding sequence and an amino acid sequence of native bovine prolactin (bPRL) have been reported; e.g. W.L. Miller et al., J. Biol. Chem., 255, 7521-24 (1980); U.S. Pat. No. 4,666,839 to Souza discloses a method for preparing bPRL by utilizing recombinant DNA methodology.
The preparation of porcine prolactin (pPRL) is well known in the art. For example, pPRL is extracted from pituitary glands of swine or can be produced via recombinant DNA technology in appropriate hosts by means well known to skilled artisans. U.S. Pat. Nos. 3,317,392 to Eppstein and 3,265,580 to Nelson et al, both incorporated by reference herein, disclose processes for preparing porcine prolactin from porcine pituitary glands. PRL can be purchased commercially from Pituitary Hormones and Antisera Center, Harbour/U.C.L.A. Medical Center, 1000 West Carson Street, Torrance, CA.
FRL produced in animals of different species vary in antigens induced, isoelectric points, N-terminal and C-terminal amino acid residues, and amino acid composition. PRL is generally species-specific that is PRL from one species is inactive or has very weak activity in another species.
This species specific limitation on the use of PRL has several disadvantages. Equipment, expertise, recombinant microorganism strains, process and handling conditions, etc. must be obtained or developed for the production of PRL for each desired species. Additionally, PRL for one species may be more costly to produce, more difficult to recover, or less stable than PRL for a different species. It would, therefore, save considerable expense and duplication of effort if, contrary to previous teachings, the PRL from one species could be used to treat other non-related species. For example, a particular advantage in costs and duplication of effort could be saved if PRL from one species could be used to promote growth in another species. Such a surprising discovery would be contrary to two prior previous teachings relating to PRL; (1) that PRL is species specific, and (2) that PRL is not an effective anabolic agent.